Ankyrin-2

Ankyrin-2 (ANK2) is a large cytoplasmic protein that functions as a crucial scaffold for organizing and stabilizing ion transporters and channels at the cell membrane (UniProt: Q01484). It mediates the localization of Na/K ATPases, Na/Ca exchangers, and other transport proteins in cardiomyocytes and skeletal muscle cells, and also participates in endocytic trafficking and cell migration through interactions with dynactin and phosphatidylinositol 3-phosphate-positive organelles.

ANK2 plays particularly important roles in cardiac and skeletal muscle function, including the regulation of sarcoplasmic reticulum organization and myocyte contraction rate. In the retina, it is similarly required for coordinated expression of ion transporters in photoreceptor cells. Mutations in ANK2 are associated with Long QT syndrome 4 (LQT4), a cardiac arrhythmia disorder characterized by repolarization defects and syncope risk.

ANK2 is classified as an SFARI category 1 gene (SFARI Cat 1), indicating it has strong evidence for involvement in autism spectrum disorder risk based on genetic findings in affected individuals.